Human β-cardiac myosin exists in an ON-state where both myosin heads are accessible for interaction with actin (Na) and an OFF-state where the heads are folded back onto their own coiledcoil tail and interacting with each other in an interacting heads motif (IHM). Hypertrophic cardiomyopathy (HCM) mutations in β-cardiac myosin cause hypercontractility of the heart. A unifying hypothesis was proposed nine years ago that the hypercontractility caused by myosin HCM mutations is primarily due to an increase in Na rather than by increases in fundamental parameters of myosin function such as intrinsic force of the motor, its velocity of movement along actin, or its ATPase turnover rate, all of which impact power output. This unifying hypothesis is revisited in light of accumulated data measuring all these parameters and the recent availability of a 3.6 Å resolution structure of the human β-cardiac myosin IHM. Biochemical measurements show that nearly all myosin HCM mutations examined show an increase in Na regardless of where they occur in the myosin head domain, consistent with the unifying hypothesis.